Lacosamide is an amino acid derivative having analgesic and anticonvulsant properties and was first reported in U.S. Pat. No. 5,773,475. According to this literature, D-serine is reacted with acetic anhydride to produce an intermediate of an N-acetyl derivative, and this intermediate is reacted with benzylamine to produce a benzylamide derivative. Then, the benzylamide derivative is O-methylated with silver (I) oxide and methyl iodide to prepare lacosamide. However, this method results in low yield, causes partial racemization in the O-methylation process, uses expensive silver (I) oxide, and thus is not suitable for mass production and industrial use.
According to the method disclosed in WO2006037574, D-serine is N-protected with a Boc (tert-butoxycarbonyl) group, followed by O-methylation. The resulting compound is reacted with benzylamine to form an amide compound, followed by N-deprotection of the Boc group and acetylation to give lacosamide. However, this reaction involves the simultaneous use of organic solvent and water, which are not well mixed, in the O-methylation process and thus requires the use of a phase transfer catalyst for efficient reaction and the use of expensive organolithium compounds. Moreover, the reaction involves the N-protection and N-deprotection of the Boc group, which prolongs the process.
In addition, according to the methods for preparing lacosamide developed so far, in order to minimize the occurrence of racemization in the O-methylation process, sterically hindered protecting groups were used for the amine of D-serine and were subjected to deprotection, and thus the preparation of lacosamide requires many processes.
Therefore, there is a need to develop a method for preparing lacosamide in a simpler, more economic and environmentally-friendly way.